Evaluation of droplet digital polymerase chain reaction by detecting cell-free deoxyribonucleic acid in pleural effusion for the diagnosis of tuberculous pleurisy: a multicentre cohort study.

OBJECTIVES: Tuberculous pleurisy is one of the most common types of extra-pulmonary tuberculosis, but the sensitivity of conventional mycobacterial culture (Culture) or Xpert MTB/RIF assay (Xpert) is not satisfying. This multicentre cohort study evaluated the accuracy of a new cell-free DNA droplet digital PCR assay (cf-ddPCR) for diagnosing tuberculous pleurisy. METHODS: Patients with suspected tuberculosis (≥5 years of age) with pleural effusion were consecutively recruited from nine research sites across six provinces in China between September 2020 to May 2022. Culture, Xpert, Xpert MTB/RIF Ultra assay (Ultra), real-time PCR, and cf-ddPCR were performed simultaneously for all specimens. RESULTS: A total of 321 participants were enrolled, and data from 281 (87.5%) participants were available, including 105 definite tuberculous pleurisy, 113 possible tuberculous pleurisy and 63 non-tuberculous pleurisy according to the composite reference standard. The sensitivity of cf-ddPCR was 90.5% (95/105, 95% CI, 82.8-95.1%) in the definite tuberculous pleurisy group, which was significantly higher than those of Culture (57.1%, 60/105, 95% CI, 47.1-66.6%, p < 0.001), Xpert (46.7%, 49/105, 95% CI, 37.0-56.6%, p < 0.001), Ultra (69.5%, 73/105, 95% CI, 59.7-77.9%, p < 0.001) and real-time PCR (75.2%, 79/105, 95% CI, 65.7-82.9%, p < 0.001). In possible tuberculous pleurisy, whose results of Culture and Xpert were both negative, the sensitivity of cf-ddPCR was 61.1% (69/113, 95% CI, 51.4-70.0%), which was still significantly higher than that of Ultra (27.4%, 31/113, 95% CI, 19.7-36.8%, p < 0.001) and real-time PCR (38.9%, 44/113, 95% CI, 30.0-48.6%, p < 0.001). DISCUSSION: The performance of cf-ddPCR is superior to Culture, Xpert, Ultra, and real-time PCR, indicating that improved diagnostic accuracy can be anticipated by incorporating this new assay.

Biomarkers Correlated with Tuberculosis Preventive Treatment Response: A Systematic Review and Meta-Analysis.

BACKGROUND: There is a need to identify alternative biomarkers to predict tuberculosis (TB) preventive treatment response because observing the incidence decline renders a long follow-up period. METHODS: We searched PubMed, Embase and Web of Science up to 9 February 2023. The biomarker levels during preventive treatment were quantitatively summarized by means of meta-analysis using the random-effect model. RESULTS: Eleven eligible studies, published during 2006-2022, were included in the meta-analysis, with frequently heterogeneous results. Twenty-six biomarkers or testing methods were identified regarding TB preventive treatment monitoring. The summarized standard mean differences of interferon-γ (INF-γ) were -1.44 (95% CI: -1.85, -1.03) among those who completed preventive treatment (τ2 = 0.21; I2 = 95.2%, p < 0.001) and -0.49 (95% CI: -1.05, 0.06) for those without preventive treatment (τ2 = 0.13; I2 = 82.0%, p < 0.001), respectively. Subgroup analysis showed that the INF-γ level after treatment decreased significantly from baseline among studies with high TB burden (-0.98, 95% CI: -1.21, -0.75) and among those with a history of Bacillus Calmette-Guérin vaccination (-0.87, 95% CI: -1.10, -0.63). CONCLUSIONS: Our results suggested that decreased INF-γ was observed among those who completed preventive treatment but not in those without preventive treatment. Further studies are warranted to explore its value in preventive treatment monitoring due to limited available data and extensive between-study heterogeneity.

A Bibliometric Analysis of Primary Aldosteronism Research From 2000 to 2020.

Thousands of papers on primary aldosteronism (PA) have been published in the last two decades. This study aimed to evaluate the research hotspots and future trends in PA research using bibliometric analysis. A total of 2,365 PA research papers between 2000 and 2020 were included. The dominant position of the United States in global PA research throughout this 20-year period was evident, and it was also the country most frequently involved in international cooperation. The University of Padua was the most productive institution and a leader in research collaboration. The Journal of Clinical Endocrinology & Metabolism was the most productive journal in terms of the number of publications on PA. Further, Mulatero P, Reincke M, Beuschlein F and Wu VC all made significant contributions to PA research. Five hotspots have been identified: (1) metabolic syndrome associated with PA; (2) molecular mechanisms of PA; (3) adrenal adenoma and adrenal cortex; (4) hypertension associated with PA; and (5) clinical monitoring parameters and diagnosis in patients with PA. Our results suggest that the molecular mechanisms of PA will remain research hotspots in the future. International collaboration is also expected to widen and deepen in the field of PA research.

Single-Cell RNA-Seq Reveals the Promoting Role of Ferroptosis Tendency During Lung Adenocarcinoma EMT Progression.

Epithelial-mesenchymal transition (EMT) and ferroptosis are two important processes in biology. In tumor cells, they are intimately linked. We used single-cell RNA sequencing to investigate the regulatory connection between EMT and ferroptosis tendency in LUAD epithelial cells. We used Seurat to construct the expression matrix using the GEO dataset GSE131907 and extract epithelial cells. We found a positive correlation between the trends of EMT and ferroptosis tendency. Then we used SCENIC to analyze differentially activated transcription factors and constructed a molecular regulatory directed network by causal inference. Some ferroptosis markers (GPX4, SCP2, CAV1) were found to have strong regulatory effects on EMT. Cell communication networks were constructed by iTALK and implied that Ferro_High_EMT_High cells have a higher expression of SDC1, SDC4, and activation of LGALS9-HARVCR2 pathways. By deconvolution of bulk sequencing, the results of CIBERSORTx showed that the co-occurrence of ferroptosis tendency and EMT may lead to tumor metastasis and non-response to immunotherapy. Our findings showed there is a strong correlation between ferroptosis tendency and EMT. Ferroptosis may have a promotive effect on EMT. High propensities of ferroptosis and EMT may lead to poor prognosis and non-response to immunotherapy.

A bibliometric analysis of testicular germ cell tumor research from 2000 to 2020.

BACKGROUND: Thousands of papers on testicular germ cell tumor (TGCT) have been published over the past two decades. This study aimed to assess the key topics and future trends in TGCT research from a comprehensive perspective. METHODS: All literature defined as review and article type on TGCT published between 2000 and 2020 was identified and retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was conducted by the online analysis platform and VOSviewer (version 1.6.16). The key directions and future trends in the research field of TGCT were evaluated using Bibliographic Item Co-occurrence Matrix Builder (version 2.0) and gCLUTO software. RESULTS: Ultimately, a total of 4,550 papers between 2000 and 2020 were included in the field of TGCT. The leadership of the United States in global TGCT research with 1,549 publications during the last two decades was obvious. The Indiana University was the most productive institution with 360 publications, and it was also the institution most frequently involved in research cooperation. Journal of Urology published the highest number of publications on TGCT. Looijenga LHJ, Bokemeyer C, Ulbright TM, Sheinfeld J and Dieckmann KP were the top productive contributors to TGCT research. Further, five research hotspots have been identified: (I) epidemiology of TGCT; (II) TGCT-related infertility; (III) pathological classification with TGCT; (IV) management options for TGCT; and (V) Prevention of cancer metastasis in TGCT patients. CONCLUSIONS: During the last two decades, the United States was a global leader, and research hotspots included epidemiology, male infertility, pathology, and therapy in the field of TGCT. Furthermore, the genetics mechanisms and cisplatin resistance will remain hotspots in future TGCT research.

Identification of prognostic chromatin-remodeling genes in clear cell renal cell carcinoma.

The aim of this study was to investigate the effects of chromatin-remodeling genes on the prognosis of patients with clear cell renal cell carcinoma (ccRCC). In TCGA-KIRC patients, two subgroups based on 86 chromatin-remodeling genes were established. The random forest algorithm was used for feature selection to identify BPTF, SIN3A and CNOT1 as characterized chromatin remodelers in ccRCC with good prognostic value. YY1 was indicated to be a transcription factor of genes highly related to BPTF, SIN3A and CNOT1. Functional annotations indicated that BPTF, SIN3A, CNOT1 and YY1 are all involved in the ubiquitin-mediated proteolysis process and that high expression of any of the five associated E3 ubiquitin ligases found in the pathway suggests a good prognosis. Protein network analysis indicated that BPTF has a targeted regulatory effect on YY1. Another independent dataset from International Cancer Genome Consortium (ICGC) showed a strong consistency with results in TCGA. In conclusion, we demonstrate that BPTF, SIN3A and CNOT1 are novel prognostic factors that predict good survival in ccRCC. We predicted that the good prognostic value of chromatin-remodeling genes BPTF and SIN3A is related to the regulation of YY1 and that YY1 regulates E3 ubiquitin ligases for further degradation of oncoproteins in ccRCC.

Novel Potential Biomarkers Associated With Epithelial to Mesenchymal Transition and Bladder Cancer Prognosis Identified by Integrated Bioinformatic Analysis.

Bladder cancer (BC) is one of the most common malignancies in terms of incidence and recurrence worldwide. The aim of this study was to identify novel prognostic biomarkers related to BC progression utilizing weighted gene co-expression network analysis (WGCNA) and further bioinformatic analysis. First, we constructed a co-expression network by using WGCNA among 274 TCGA-BLCA patients and preliminarily screened out four genes (CORO1C, TMPRSS4, PIK3C2B, and ZNF692) associated with advanced clinical traits. In support, GSE19915 and specimens from 124 patients were used to validate the genes selected by WGCNA; then, CORO1C and TMPRSS4 were confirmed as hub genes with strong prognostic values in BC. Moreover, the result of gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) indicated that CORO1C and TMPRSS4 might be involved in the process of epithelial to mesenchymal transition (EMT) reversely. In addition, high expression of CORO1C was found to be significantly correlated with tumor-infiltrating neutrophils (TINs), a negative regulatory component that facilitates tumor distant progression and induces poor clinical outcome. In conclusion, our study first identified CORO1C and TMPRSS4 as vital regulators in the process of tumor progression through influencing EMT and could be developed to effective prognostic and therapeutic targets in future BC treatment.